Abstract / Project Summary Evaluations of treatments for substance use disorders (SUDs) have predominantly focused on abstinence-based primary outcomes, an approach that does not encompass the functional status of patients who may reduce drug use and experience improvements in health and other functional domains. Identification of diverse, clinically relevant outcomes for use in future research may advance treatment development for SUDs. In response to PA 15-099 (Reductions in Illicit Drug Use and Functional Outcomes, R21/R33), this project will determine if reductions in cannabis use are associated with positive changes in health, psychosocial, and other functional outcomes in individuals with cannabis use disorder (CUD). The project will first conduct 2 years of R21 exploratory work followed by 3 years of R33 research to establish the relationships between reduced cannabis use and improved functional outcomes that are clinically meaningful. The aims of the R21 study are: Aim 1. Explore potential functional outcomes across multiple domains by retrospectively assessing changes in functional status in association with changes in cannabis use among CUD patients; functional domains that improve with reduced cannabis use will be identified for further consideration. Aim 2. Identify promising functional outcomes for further examination by prospectively assessing relationships between patterns of cannabis use and changes in functional outcomes among treatment-seeking CUD patients, and establish feasibility of assessments and procedures in preparation for the R33. Effect sizes will be estimated for functional outcomes that improve with reduced cannabis use over a short period of observation. Promising functional outcomes identified in the R21 phase will be examined for their relevance and predictive validity in the R33 phase in a larger sample over a longer period of observation. The aims of the R33 study are: Aim 1. Determine functional outcomes that demonstrate clinically meaningful improvement in association with reduced cannabis use. Aim 2. Identify levels and frequencies of cannabis use associated with clinically meaningful improvements in functional outcomes by prospectively examining relationships between cannabis use patterns and changes in functional outcomes over time among treatment-seeking CUD patients. Aim 3 (Exploratory). Identify patient characteristics (e.g., gender, race/ethnicity) and comorbid medical and psychiatric conditions that influence such relationships. The proposed study will efficiently identify functional outcomes demonstrating clinically meaningful improvement in association with reduced cannabis use by using innovative methodologies and longitudinal approaches to systematically assess multiple functional domains (health, mental health, social health, cognitive function, HIV risk, quality of life), and by applying multiple measurement methods (biomedical, self-report) and advanced statistical approaches. Project findings will inform considerations of reduction in cannabis use as a valid outcome measure in clinical intervention trials for CUD.